Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells |
| |
| Authors: | Kumar Sarvesh Singh Brajendra K Arya Pragya Malhotra Shashwat Thimmulappa Rajesh Prasad Ashok K Van der Eycken Erik Olsen Carl E DePass Anthony L Biswal Shyam Parmar Virinder S Ghosh Balaram |
| |
| Affiliation: | aMolecular Immunogenetics Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India;bDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;cBioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India;dLaboratory for Organic Synthesis, Department of Chemistry, University of Leuven, Celeslinjenlaan 200F, B-3001 Heverlee, Belgium;eDepartment of Basic Sciences and Environment, University of Copenhagen, DK-1871 Frederiksberg C, Denmark;fDepartment of Biology, Long Island University, DeKalb Avenue, Brooklyn, NY 11201, USA |
| |
| Abstract: | In the present study, we report the design and synthesis of novel analogs of cinnamates, thiocinnamates and thionocinnamates and evaluated the potencies of these analogs to inhibit TNF-α induced ICAM-1 expression on human endothelial cells. By using whole cell-ELISA, our screening data demonstrated that ethyl 3′,4′,5′-trimethoxythionocinnamate (ETMTC) is the most potent inhibitor of TNF-α induced ICAM-1, VCAM-1 and E-selectin. As functional consequences, ETMTC abrogated TNF-α induced adhesion of neutrophils to the endothelial monolayer. Structure–activity relationship studies revealed the critical role of the chain-length of the alkyl group in the alcohol moiety, number of methoxy groups in the aromatic ring of the cinnamoyl moiety and the presence of the α, β- C–C double bond in the thiocinnamates and thionocinnamates. |
| |
| Keywords: | Cinnamates Thiocinnamates thionocinnamates Cell adhesion molecules Endothelial cells |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
